The objectives of this grant are to delineate the mechanisms of development of immediate hypersensitivity. These goals include the design of investigative models both in animals and man to study the genetic and environmental factors important in the development of immediate hypersensitivity. Inbred rats will be used as an animal model to study the immunogenetic and ontogenetic controls involved in reaginic antibody synthesis; because preliminary studies in our laboratory have shown that after immunization with the same antigen inbred BN rats synthesize reagins, whereas inbred ACI rats do not. The hereditary pattern of this genetic trait will be determined in appropriate breeding experiments with these two strains of rats. In addition, the immunogenicity of various antigens, including synthetic polypeptides, to induce reagin synthesis and the adjuvant effect of parasites on reagin synthesis will be explored in both inbred and outbred rats. The ontogenetic requirements, including reagin synthesis, for the development of immediate hypersensitivity will be studied in rats of various ages. In humans, the immunogenicity of tetanus and diphtheria toxoids, which are used in routine immunization programs, will be examined in order to define the patterns of synthesis of reaginic antibody and other immunoglobulins. Preliminary studies in our laboratory and by others have suggested that reaginic antibody is more frequently demonstrable in atopic individuals than in normal subjects. This capacity to induce reagins will be correlated with the incidence and future development of atopic disease in order to define hereditary patterns and to develop a predictive test for the development of immediate hypersensitivity syndromes. In addition, these studies may define the role of alum adjuvants, pertussis vaccine and repeated immunization with small doses of antigen, factors shown to enhance reaginic antibody synthesis in animals, on reagin synthesis in humans.